TY - JOUR
T1 - Effect of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8- yl)-1-propanone fumarate, a novel acetylcholinesterase inhibitor, on spatial cognitive impairment induced by chronic cerebral hypoperfusion in rats
AU - Xu, A. Jing
AU - Chen, Zhong
AU - Yanai, Kazuhiko
AU - Huang, Yu Wen
AU - Wei, Er Qing
N1 - Funding Information:
This project was supported by the National Natural Science Foundation of China (No 30000019) and Zhejiang Provincial Natural Science Foundation of China (No 300062), and partly supported by the Scientific Research Foundations for the Returned Overseas Chinese Scholars.
PY - 2002/10/4
Y1 - 2002/10/4
N2 - It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8- yl)-1-propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil.
AB - It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8- yl)-1-propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil.
KW - 2,3,5-Triphenyltetrazolium
KW - Cerebral ischemia
KW - Cholinesterase inhibitor
KW - Memory deficit
KW - TAK-147
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U2 - 10.1016/S0304-3940(02)00830-3
DO - 10.1016/S0304-3940(02)00830-3
M3 - Article
C2 - 12359317
AN - SCOPUS:0037020523
VL - 331
SP - 33
EP - 36
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 1
ER -